Project summary Behavioral strategies to cope with potentially threatening or aversive stimuli tend to cluster into two forms: active, escape-driven behaviors, or passive responses that may conserve energy or prevent detection by a predator. Since an individual's coping strategy is closely linked to long-term clinical outcomes after trauma exposure, a better understanding of the neurobiological basis of coping response could greatly impact public health for both men and women. One promising but under-studied area is the role of the endocannabinoid (eCB) system in modulating active vs. passive stress responses. In this project, we will define the contribution of eCB signaling in the medial prefrontal cortex (mPFC) to the mechanisms that underlie coping responses in both sexes. In particular, we will investigate the ability of eCB system to modulate two mPFC-brainstem pathways: mPFC-dorsal raphe (DR) and mPFC-periaqueductal gray (PAG). We will use a combination of behavioral, neuroanatomical, biochemical, and chemogenetic strategies to dissect these circuits. The results of this work will lead to a better understanding of sex-specific stress processes, and have the potential to identify novel therapeutic targets for stress-related mental illnesses.